A Novel APOC2 Mutation in a Colombian Patient with Recurrent Hypertriglyceridemic Pancreatitis

Abstract

Hypertriglyceridemia is a common disease with only 2% of cases exhibiting monogenic mutations. Familial chylomicronemia syndrome (FCS) is a rare genetic condition associated with recurrent and severe episodes of pancreatitis and is mainly caused by mutations in the LPL gene, with few cases related to abnormal function of apolipoprotein C-II. This is a 50-year-old female with a past medical history of arterial hypertension, miscarriage and recurrent pancreatitis. In the last four years, her triglycerides and lipase concentration reached >3000 mg/dL and >700 U/L, respectively. The patient was not responsive to statins, fibrates, or tetrahydrolipstatin. A novel homozygous frameshift mutation on exon 3 of the APOC2 gene was detected, c.133_134delTC. Subsequent Sanger sequencing confirmed that three first-degree relatives were carriers of the same mutation. To the best of our knowledge, we are reporting the first Colombian patient with FCS due to an APOC2 mutation. We propose that this mutation caused recurrent hypertriglyceridemic pancreatitis.

Keywords: apolipoprotein C-II; hyperlipoproteinemia type I; hypertriglyceridemia; pancreatitis.

Figure 1

Laboratory and imaging findings. (A) Creamy supernatant from drawn blood. (B) Progression of serum concentrations over time for TG, total cholesterol and lipase. Star (*) specifies heparin infusion and error bars represent interquartile range (TG n=6, lipase n=2). (C) Coronal MRI showing acute pancreatitis. Arrows designate inflammatory plastron.

Figure 2

APOC2 protein scheme and three-dimensional visualization via Swiss-PDB Viewer. (A) Wild-type APOC2 protein. The purple polygons indicate the signal peptide domain. H1: helix 1; H2: helix 2; H3: helix 3. (B) Suggested structure of mutated APOC2 protein (p.Ser45Glnfs*24). The structure variation due to a frameshift mutation in protein is shown. In red: the aminoacid change; light color: the regions lost due to the premature stop codon.

Figure 3

Family pedigree and Sanger sequencing. (A) Pedigree demonstrating consanguineous relationship in the patients’ parents and carrier status of the frameshift mutation c.133_134delTC in exon 3 of the APOC2 gene. Arrow: index case; black symbol: familial chylomicronemia syndrome; black dot: heterozygous carriers (B) Sanger sequencing electropherogram of the patient and carriers of the frameshift mutation in the APOC2 gene.